Characterising private and shared signatures of positive selection in 37 Asian populations.
ABSTRACT: The Asian Diversity Project (ADP) assembled 37 cosmopolitan and ethnic minority populations in Asia that have been densely genotyped across over half a million markers to study patterns of genetic diversity and positive natural selection. We performed population structure analyses of the ADP populations and divided these populations into four major groups based on their genographic information. By applying a highly sensitive algorithm haploPS to locate genomic signatures of positive selection, 140 distinct genomic regions exhibiting evidence of positive selection in at least one population were identified. We examined the extent of signal sharing for regions that were selected in multiple populations and observed that populations clustered in a similar fashion to that of how the ancestry clades were phylogenetically defined. In particular, populations predominantly located in South Asia underwent considerably different adaptation as compared with populations from the other geographical regions. Signatures of positive selection present in multiple geographical regions were predicted to be older and have emerged prior to the separation of the populations in the different regions. In contrast, selection signals present in a single population group tended to be of lower frequencies and thus can be attributed to recent evolutionary events.
Project description:The analysis of geographically specific regions and the characterization of fine-scale patterns of genetic diversity may facilitate a much better understanding of the microevolutionary processes affecting local human populations. Here we generated genome-wide high-density SNP genotype data in 425 individuals from six geographical regions in Lithuania and combined our dataset with available ancient and modern data to explore genetic population structure, ancestry components and signatures of natural positive selection in the Lithuanian population. Our results show that Lithuanians are a homogenous population, genetically differentiated from neighbouring populations but within the general expected European context. Moreover, we not only confirm that Lithuanians preserve one of the highest proportions of western, Scandinavian and eastern hunter-gather ancestry components found in European populations but also that of an steppe Early to Middle Bronze Age pastoralists, which together configure the genetic distinctiveness of the Lithuanian population. Finally, among the top signatures of positive selection detected in Lithuanians, we identified several candidate genes related with diet (PNLIP, PPARD), pigmentation (SLC24A5, TYRP1 and PPARD) and the immune response (BRD2, HLA-DOA, IL26 and IL22).
Project description:Affymetrix single nucleotide polymorphism (SNP) array data were collected to study genome-wide patterns of genomic variation across a broad geographical range of Island Southeast Asian populations. This region has experienced an extremely complex admixture history. Initially settled ~50,000 years ago, Island Southeast Asia has since been the recipient of multiple waves of population movements, most recently by Austronesian-speaking groups ultimately from Neolithic mainland Asia and later arrivals during the historic era from India and the Middle East. We have genotyped SNPs in ~500 individuals from 30 populations spanning this entire geographical region, from communities close to mainland Asia through to New Guinea. Particular attention has been paid to genomic data that are informative for population history, including the role of recent arrivals during the historic era and admixture with archaic hominins. Overall design: 506 samples from 30 populations has been genotyped using the Affymetrix platform GPL18441
Project description:BACKGROUND: The HUGO Pan-Asian SNP Consortium (PASNP) has generated a genetic resource of almost 55,000 autosomal single nucleotide polymorphisms (SNPs) across more than 1,800 individuals from 73 urban and indigenous populations in Asia. This has offered valuable insights into the correlation between the genetic ancestry of these populations with major linguistic systems and geography. Here, we attempt to understand whether adaptation to local climate, diet and environment partly explains the genetic variation present in these populations by investigating the genomic signatures of positive selection. RESULTS: To evaluate the impact to the selection analyses due to the considerably lower SNP density as compared to other population genetics resources such as the International HapMap Project (HapMap) or the Singapore Genome Variation Project, we evaluated the extent of haplotype phasing switch errors and the consistency of selection signals from three haplotype-based approaches (iHS, XP-EHH, haploPS) when the HapMap data is thinned to a similar density as PASNP. We subsequently applied haploPS to detect and characterize positive selection in the PASNP populations, identifying 59 genomics regions that were selected in at least one PASNP populations. A cluster analysis on the basis of these 59 signals showed that indigenous populations such as the Negrito from Malaysia and Philippines, the China Hmong, and the Taiwan Ami and Atayal shared more of these signals. We also reported evidence of a positive selection signal encompassing the beta globin gene in the Taiwan Ami and Atayal that was distinct from the signal in the HapMap Africans, suggesting the possibility of convergent evolution at this locus due to malarial selection. CONCLUSIONS: We established that the lower SNP content of the PASNP data conferred weaker ability to detect signatures of positive selection, but the availability of the new approach haploPS retained modest power. Out of all the populations in PASNP, we identified only 59 signals, suggesting a strong need for high-density population-level genotyping data or sequencing data in order to achieve a comprehensive survey of positive selection in Asian populations.
Project description:DENV-2 spread throughout the tropical and subtropical regions globally, which is implicated in deadly outbreaks of DHF and DSS. Since dengue cases have grown dramatically in recent years, about half of the world's population is now at risk. Our timescale analysis indicated that the most recent common ancestor existed about 100 years ago. The rate of nucleotide substitution was estimated to be 8.94?×?10-4 subs/site/year. Selection pressure analysis showed that two sites 160 and 403 were under positive selection, while E gene is mainly shaped by stronger purifying selection. BSP analysis showed that estimating effective population size from samples of sequences has undergone three obvious increases, additionally, Caribbean and Puerto Rico maintained higher levels of genetic diversity relative to other 6 representative geographical populations using GMRF method. The phylogeographic analysis indicated that two major transmission routes are from South America to Caribbean and East&SouthAsia to Puerto Rico. The trunk reconstruction confirmed that the viral evolution spanned 50 years occurred primarily in Southeast Asia and East&South Asia. In addition, phylogeographic association-trait analysis indicated that the viral phenotypes are highly correlated with phylogeny in Nicaragua and Puerto Rico (P?<?0.05).
Project description:We explored possible links between vector activity and genetic diversity in introduced populations of Limnoperna fortunei by characterizing the genetic structure in native and introduced ranges in Asia and South America. We surveyed 24 populations: ten in Asia and 14 in South America using the mitochondrial cytochrome c oxidase subunit I (COI) gene, as well as eight polymorphic microsatellite markers. We performed population genetics and phylogenetic analyses to investigate population genetic structure across native and introduced regions. Introduced populations in Asia exhibit higher genetic diversity (H(E)?=?0.667-0.746) than those in South America (H(E)?=??0.519-0.575), suggesting higher introduction effort for the former populations. We observed pronounced geographical structuring in introduced regions, as indicated by both mitochondrial and nuclear markers based on multiple genetic analyses including pairwise ?(ST), F(ST), bayesian clustering method, and three-dimensional factorial correspondence analyses. Pairwise F(ST) values within both Asia (F(ST)?=?0.017-0.126, P?=?0.000-0.009) and South America (F(ST)?=0.004-0.107, P?=?0.000-0.721) were lower than those between continents (F(ST)?=?0.180-0.319, P?=?0.000). Fine-scale genetic structuring was also apparent among introduced populations in both Asia and South America, suggesting either multiple introductions of distinct propagules or strong post-introduction selection and demographic stochasticity. Higher genetic diversity in Asia as compared to South America is likely due to more frequent propagule transfers associated with higher shipping activities between source and donor regions within Asia. This study suggests that the intensity of human-mediated introduction vectors influences patterns of genetic diversity in non-indigenous species.
Project description:Dromedary camels (Camelus dromedarius) are single-humped animals found throughout the deserts of Africa, the Arabian Peninsula, and the southwest of Asia. This well-adapted species is mainly used for milk and meat production, although some specific types exhibit superior running performance and are used in racing competitions. However, neither performance nor production camels are bred under intensive genomic selection programs with specific aims to improve these traits. In this study, the full genome sequence data of six camels from the Arabian Peninsula and the genotyping-by-sequencing data of 44 camels (29 packing and 15 racing) from Sudan were analyzed to assess their genome diversities, relationships, and candidate signatures of positive selection. Genome ADMIXTURE and principle component analyses indicate clear geographic separation between the Sudanese and the Arabian Peninsula camels, but with no population-specific genetic distinction within populations. Camel samples from the Arabian Peninsula show higher mean heterozygosity (0.560 ± 0.003) than those from Sudan (0.347 ± 0.003). Analyses of signatures of selection, using pooled heterozygosity (Hp) approach, in the Sudanese camels revealed 176, 189, and 308 candidate regions under positive selection in the combined and packing and racing camel populations, respectively. These regions host genes that might be associated with adaptation to arid environment, dairy traits, energy homeostasis, and chondrogenesis. Eight regions show high genetic differentiation, based on Fst analysis, between the Sudanese packing and racing camel types. Genes associated with chondrogenesis, energy balance, and urinary system development were found within these regions. Our results advocate for further detailed investigation of the genome of the dromedary camel to identify and characterize genes and variants associated with their valuable phenotypic traits. The results of which may support the development of breeding programs to improve the production and performance traits of this unique domesticated species.
Project description:Recent reports have identified a north-south cline in genetic variation in East and South-East Asia, but these studies have not formally explored the basis of these clinical differences. Understanding the origins of these variations may provide valuable insights in tracking down the functional variants in genomic regions identified by genetic association studies. Here we investigate the genetic basis of these differences with genome-wide data from the HapMap, the Human Genome Diversity Project and the Singapore Genome Variation Project. We implemented four bioinformatic measures to discover genomic regions that are considerably differentiated either between two Han Chinese populations in the north and south of China, or across 22 populations in East and South-East Asia. These measures prioritized genomic stretches with: (i) regional differences in the allelic spectrum for SNPs common to the two Han Chinese populations; (ii) differential evidence of positive selection between the two populations as quantified by integrated haplotype score (iHS) and cross-population extended haplotype homozygosity (XP-EHH); (iii) significant correlation between allele frequencies and geographical latitudes of the 22 populations. We also explored the extent of linkage disequilibrium variations in these regions, which is important in combining genetic association studies from North and South Chinese. Two of the regions that emerged are found in HLA class I and II, suggesting that the HLA imputation panel from the HapMap may not be directly applicable to every Chinese sample. This has important implications to autoimmune studies that plan to impute the classical HLA alleles to fine map the SNP association signals.
Project description:BACKGROUND:HIV susceptibility and pathogenicity exhibit both interindividual and intergroup variability. The etiology of intergroup variability is still poorly understood, and could be partly linked to genetic differences among racial/ethnic groups. These genetic differences may be traceable to different regimes of natural selection in the 60,000 years since the human radiation out of Africa. Here, we examine population differentiation and haplotype patterns at several loci identified through genome-wide association studies on HIV-1 control, as determined by viral-load setpoint, in European and African-American populations. We use genome-wide data from the Human Genome Diversity Project, consisting of 53 world-wide populations, to compare measures of FST and relative extended haplotype homozygosity (REHH) at these candidate loci to the rest of the respective chromosome. RESULTS:We find that the Europe-Middle East and Europe-South Asia pairwise FST in the most strongly associated region are elevated compared to most pairwise comparisons with the sub-Saharan African group, which exhibit very low FST. We also find genetic signatures of recent positive selection (higher REHH) at these associated regions among all groups except for sub-Saharan Africans and Native Americans. This pattern is consistent with one in which genetic differentiation, possibly due to diversifying/positive selection, occurred at these loci among Eurasians. CONCLUSIONS:These findings are concordant with those from earlier studies suggesting recent evolutionary change at immunity-related genomic regions among Europeans, and shed light on the potential genetic and evolutionary origin of population differences in HIV-1 control.
Project description:The Asian Diversity Project (ADP) assembled 37 cosmopolitan and ethnic minority populations in Asia that have been densely genotyped across over half a million markers to study patterns of genetic diversity and positive natural selection.
Project description:Background:Anthropogenic factors potentially affect observed biogeographical patterns in population genetics, but the effects of ancient human activities on the original patterns created by natural processes are unknown. Sinotaia quadrata, a widely distributed freshwater snail species in East Asia, was used to investigate this issue. It is unclear whether S. quadrata in Japan was introduced from China and how different human uses and varying geographic patterns affect the contemporary population genetics between the two regions. Thus, we investigated the demography of S. quadrata and detected its genetic structure in Japan and continental East Asia. Results:Sinotaia quadrata populations first naturally migrated from continental East Asia to Japan, which is associated with the ancient period in Japanese geohistory (about 70,000 years ago). They were then artificially introduced in association with agriculture expansion by human movements in two recent periods (about 8,000 and 1,200 years ago). Populations in different parts of Japan have their own sources. Natural migration in the ancient period and artificial introduction in the recent period suggest that the population distribution is affected by both the geohistory of East Asia and the history of human expansion. In the background of the historical migration and introduction, contemporary populations in the two regions show different genetic patterns. Population divergence levels were significantly correlated with geographical patterns in Japan and significantly correlated with human interventions variables in continental East Asia, suggesting that long-term geographical isolation is likely the major factor that shaped the contemporary population genetics in Japan, while modern human uses are likely the major factor in continental East Asia. Conclusions:Our preliminary results show a complex demography and unusual genetic patterns in the contemporary populations for a common freshwater snail and are of significance to determine the historical formation and contemporary patterns of biogeography in Japan and continental East Asia.